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The metalloproteinase papp-aa controls epithelial cell quiescence-proliferation transition

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The metalloproteinase papp-aa controls epithelial cell quiescence-proliferation transition. / Liu, Chengdong; Li, Shuang; Noer, Pernille Rimmer et al.

In: eLife, Vol. 9, e52322, 04.2020.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Harvard

Liu, C, Li, S, Noer, PR, Kjaer-Sorensen, K, Juhl, AK, Goldstein, A, Ke, C, Oxvig, C & Duan, C 2020, 'The metalloproteinase papp-aa controls epithelial cell quiescence-proliferation transition', eLife, vol. 9, e52322. https://doi.org/10.7554/eLife.52322

APA

Liu, C., Li, S., Noer, P. R., Kjaer-Sorensen, K., Juhl, A. K., Goldstein, A., Ke, C., Oxvig, C., & Duan, C. (2020). The metalloproteinase papp-aa controls epithelial cell quiescence-proliferation transition. eLife, 9, [e52322]. https://doi.org/10.7554/eLife.52322

CBE

Liu C, Li S, Noer PR, Kjaer-Sorensen K, Juhl AK, Goldstein A, Ke C, Oxvig C, Duan C. 2020. The metalloproteinase papp-aa controls epithelial cell quiescence-proliferation transition. eLife. 9:Article e52322. https://doi.org/10.7554/eLife.52322

MLA

Liu, Chengdong et al. "The metalloproteinase papp-aa controls epithelial cell quiescence-proliferation transition". eLife. 2020. 9. https://doi.org/10.7554/eLife.52322

Vancouver

Liu C, Li S, Noer PR, Kjaer-Sorensen K, Juhl AK, Goldstein A et al. The metalloproteinase papp-aa controls epithelial cell quiescence-proliferation transition. eLife. 2020 Apr;9:e52322. doi: 10.7554/eLife.52322

Author

Liu, Chengdong ; Li, Shuang ; Noer, Pernille Rimmer et al. / The metalloproteinase papp-aa controls epithelial cell quiescence-proliferation transition. In: eLife. 2020 ; Vol. 9.

Bibtex

@article{5eba4e29ee664bb2bb10286b9201226b,
title = "The metalloproteinase papp-aa controls epithelial cell quiescence-proliferation transition",
abstract = "Human patients carrying PAPP-A2 inactivating mutations have low bone mineral density. The underlying mechanisms for this reduced calcification are poorly understood. Using a zebrafish model, we report that Papp-aa regulates bone calcification by promoting Ca2+-transporting epithelial cell (ionocyte) quiescence-proliferation transition. Ionocytes, which are normally quiescent, re-enter the cell cycle under low [Ca2+] stress. Genetic deletion of Papp-aa, but not the closely related Papp-ab, abolished ionocyte proliferation and reduced calcified bone mass. Loss of Papp-aa expression or activity resulted in diminished IGF1 receptor-Akt-Tor signaling in ionocytes. Under low Ca2+ stress, Papp-aa cleaved Igfbp5a. Under normal conditions, however, Papp-aa proteinase activity was suppressed and IGFs were sequestered in the IGF/Igfbp complex. Pharmacological disruption of the IGF/Igfbp complex or adding free IGF1 activated IGF signaling and promoted ionocyte proliferation. These findings suggest that Papp-aa-mediated local Igfbp5a cleavage functions as a [Ca2+]-regulated molecular switch linking IGF signaling to bone calcification by stimulating epithelial cell quiescence-proliferation transition under low Ca2+ stress.",
author = "Chengdong Liu and Shuang Li and Noer, {Pernille Rimmer} and Kasper Kjaer-Sorensen and Juhl, {Anna Karina} and Allison Goldstein and Caihuan Ke and Claus Oxvig and Cunming Duan",
year = "2020",
month = apr,
doi = "10.7554/eLife.52322",
language = "English",
volume = "9",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications Ltd.",

}

RIS

TY - JOUR

T1 - The metalloproteinase papp-aa controls epithelial cell quiescence-proliferation transition

AU - Liu, Chengdong

AU - Li, Shuang

AU - Noer, Pernille Rimmer

AU - Kjaer-Sorensen, Kasper

AU - Juhl, Anna Karina

AU - Goldstein, Allison

AU - Ke, Caihuan

AU - Oxvig, Claus

AU - Duan, Cunming

PY - 2020/4

Y1 - 2020/4

N2 - Human patients carrying PAPP-A2 inactivating mutations have low bone mineral density. The underlying mechanisms for this reduced calcification are poorly understood. Using a zebrafish model, we report that Papp-aa regulates bone calcification by promoting Ca2+-transporting epithelial cell (ionocyte) quiescence-proliferation transition. Ionocytes, which are normally quiescent, re-enter the cell cycle under low [Ca2+] stress. Genetic deletion of Papp-aa, but not the closely related Papp-ab, abolished ionocyte proliferation and reduced calcified bone mass. Loss of Papp-aa expression or activity resulted in diminished IGF1 receptor-Akt-Tor signaling in ionocytes. Under low Ca2+ stress, Papp-aa cleaved Igfbp5a. Under normal conditions, however, Papp-aa proteinase activity was suppressed and IGFs were sequestered in the IGF/Igfbp complex. Pharmacological disruption of the IGF/Igfbp complex or adding free IGF1 activated IGF signaling and promoted ionocyte proliferation. These findings suggest that Papp-aa-mediated local Igfbp5a cleavage functions as a [Ca2+]-regulated molecular switch linking IGF signaling to bone calcification by stimulating epithelial cell quiescence-proliferation transition under low Ca2+ stress.

AB - Human patients carrying PAPP-A2 inactivating mutations have low bone mineral density. The underlying mechanisms for this reduced calcification are poorly understood. Using a zebrafish model, we report that Papp-aa regulates bone calcification by promoting Ca2+-transporting epithelial cell (ionocyte) quiescence-proliferation transition. Ionocytes, which are normally quiescent, re-enter the cell cycle under low [Ca2+] stress. Genetic deletion of Papp-aa, but not the closely related Papp-ab, abolished ionocyte proliferation and reduced calcified bone mass. Loss of Papp-aa expression or activity resulted in diminished IGF1 receptor-Akt-Tor signaling in ionocytes. Under low Ca2+ stress, Papp-aa cleaved Igfbp5a. Under normal conditions, however, Papp-aa proteinase activity was suppressed and IGFs were sequestered in the IGF/Igfbp complex. Pharmacological disruption of the IGF/Igfbp complex or adding free IGF1 activated IGF signaling and promoted ionocyte proliferation. These findings suggest that Papp-aa-mediated local Igfbp5a cleavage functions as a [Ca2+]-regulated molecular switch linking IGF signaling to bone calcification by stimulating epithelial cell quiescence-proliferation transition under low Ca2+ stress.

UR - http://www.scopus.com/inward/record.url?scp=85084167042&partnerID=8YFLogxK

U2 - 10.7554/eLife.52322

DO - 10.7554/eLife.52322

M3 - Journal article

C2 - 32293560

AN - SCOPUS:85084167042

VL - 9

JO - eLife

JF - eLife

SN - 2050-084X

M1 - e52322

ER -